NUTLEY, N.J., May 22 /PRNewswire/ -- Hoffmann-La Roche announced
today it has submitted a Biologics License Application (BLA) to the
U.S. Food and Drug Administration (FDA) for approval to market
PEGASYS(TM) (peginterferon alfa-2a) for the treatment of chronic
hepatitis C in non-cirrhotic and cirrhotic patients with
compensated liver disease.

In clinical studies to date, PEGASYS has attained response rates
that may be in the same range as those reported with currently
available combination therapy. Clinical studies have demonstrated
favorable results versus monotherapy with standard interferon, even
in cirrhotic patients, the most difficult to treat. PEGASYS, a
ready-to-use solution, is expected to be administered as a
once-weekly subcutaneous injection taken for one year, in
comparison to standard interferon, which must be taken three times
per week.

"PEGASYS is backed by ten years of Roche research in
sophisticated drug design," said Myron Holubiak, president, Roche
Laboratories. "If approved, it will bolster the hepatitis C
marketplace by giving potentially hundreds of thousands of patients
in the U.S. a desperately-needed therapy option. It could be an
important advance that may ultimately provide patients with
impressive response rates and the convenience of once-weekly
injections."

Clinical Data
A pegylated interferon, PEGASYS is a longer-lasting form of
interferon for the treatment of hepatitis C virus (HCV). In
rigorous intent-to-treat analyses of three pivotal clinical studies
involving a total of more than 1,400 patients, those treated with
180 mcg. of PEGASYS had overall sustained virological responses of
35 percent in patients without cirrhosis and 30 percent in patients
with cirrhosis. Virological response was defined as undetectable
HCV RNA as measured by the AMPLICOR HCV Monitor(TM), version 2.0.
Standard interferon therapy has proven effective in only 11-19
percent of hepatitis C patients in the general population and in 5
percent or less of patients with cirrhosis.

In the largest prospective study (n=271) to include only
hepatitis C patients with cirrhosis - the most difficult group of
hepatitis C patients to treat - data showed that PEGASYS may
achieve a sustained response rate nearly four times higher than
standard interferon - 30 percent (26 of 87) verses 8 percent (7 of
88).

In addition, data from two other studies show that patients
treated with PEGASYS exhibited improved liver histology in
post-treatment liver biopsies. In a study examining 184 adult
hepatitis C patients with cirrhosis, 54 percent (37 of 68) who
received 180 mcg. of PEGASYS demonstrated a histological response,
while only 31 percent (17 of 55) of participants in the standard
interferon arm demonstrated a similar response. In a study
examining histology in non-cirrhotics, 63 percent (19 of 30) of
patients who received 180 mug. of PEGASYS demonstrated a
histological response, versus 57 percent (13 of 23) who received
standard interferon. Many researchers believe improved histology
may be associated with slowing the progression of liver
disease.

"Physicians have very few weapons in their arsenal against
hepatitis C," said Mitchell Shiffman, MD, chief, Hepatology
Section, Medical College of Virginia. "In clinical studies I've
conducted, in addition to seeing response rates several times
higher than those attained with standard interferon, patients are
able to maintain their daily routine, without living their lives
around the three-times-per week injections required of standard
interferon."

Adverse events with PEGASYS are similar to those seen with
standard interferon regimens, such as fatigue, headache,
myalgia/arthralgia, flu-like symptoms, nausea/vomiting, fever,
chills, diarrhea, partial alopecia, abdominal pain, depression,
irritability, insomnia, and anorexia.

About Pegylation
PEGASYS is made when interferon alfa-2a undergoes the process of
pegylation, in which one or more chains of polyethylene glycol
(also known as PEG) are attached to another molecule. In PEGASYS, a
large, branched, mobile PEG is covalently bound to the interferon
alfa-2a molecule and provides a selectively protective barrier,
without significantly reducing binding site receptivity.
Pharmacokinetic behavior of a pegylated molecule depends on the
length of the PEG and the structure of the link between the PEG
moiety and the protein. Researchers believe the PEG creates a
barrier that shields the interferon alfa-2a from being eliminated
from the body too rapidly and maintains its ability to consistently
suppress the hepatitis C virus over the one week dosing period.
Specifically, clinical trials have demonstrated that PEGASYS may
provide longer-lasting levels of drug in the blood -- drug levels
following a single dose of PEGASYS last more than one full week
(168 hours) as compared to less than 24 hours with standard
interferon.

The high molecular weight (40 kilodalton) branched PEG in
PEGASYS is believed to provide sustained pegylated interferon
alfa-2a exposure at clinically effective levels over the one week
dosing period. In contrast, interferons with smaller PEGs are
excreted quickly by the kidneys, requiring more frequent dosing,
according to earlier Roche studies, using smaller PEGs developed by
the company.

The specific "PEG" used in PEGASYS was licensed by Roche from
Shearwater Polymers, Inc., in Huntsville, Alabama.

Quality of Life Data
In addition to the virologic and histologic results reported for
PEGASYS trials, a self-rated health improvement survey evaluating
the quality of life (QoL) of patients with chronic hepatitis C
showed improved scores among those treated with once-weekly doses
of PEGASYS versus those treated with thrice-weekly doses of
standard interferon alfa-2a. Because its symptoms are often
debilitating -- including lethargy, loss of appetite, nausea and
vomiting, fever and joint pain - chronic hepatitis C can have a
profound effect on health-related QoL. Results were collected in a
randomized, controlled clinical trial (n=250) comparing PEGASYS to
standard interferon. When asked to rate their general health
compared to one year before, 48 percent of patients treated with
PEGASYS reported feeling better or much better, compared to 26
percent for standard interferon. The QoL data were presented this
week at Digestive Disease Week in San Diego.

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver, is a
leading cause of cirrhosis and liver cancer and the number-one
reason for liver transplants in the U.S. An estimated four million
Americans are infected with the virus, with approximately 35,000
new infections each year. In the United States, the Centers for
Disease Control and Prevention estimate that hepatitis C is
responsible for eight to ten thousand deaths per year and could
increase to 38,000 by the year 2010, surpassing annual HIV/AIDS
deaths.

Hepatitis C is a blood-borne virus transmitted through body
fluids, primarily blood or blood products, and sharing needles. In
many patients, the mode of transmission is unknown. Unfortunately,
most people who are infected with hepatitis C are unaware of it
because, like HIV, it may take years for symptoms to develop. In
addition, it is estimated that as many as 40 percent of people with
HIV may be co-infected with hepatitis C.

About Hoffmann-La Roche, Inc.
Hoffmann-La Roche Inc. (Roche) based in Nutley, N.J., is the U.S.
prescription drug unit of the Roche Group, a leading research-based
health care enterprise that ranks among the world's leaders in
pharmaceuticals, diagnostics, vitamins, and fragrances and flavors.
Roche discovers, develops, manufactures and markets numerous
important prescription drugs that enhance people's health,
well-being and quality of life. Among the company's areas of
therapeutic interest are: virology, including HIV/AIDS and
hepatitis C; infectious diseases, including influenza; cardiology;
neurology; oncology; transplantation; dermatology; and metabolic
diseases including obesity and diabetes.

For more information on the Roche pharmaceuticals business in
the United States, visit the company's web site at:
http://www.rocheusa.com.